Ligation of MHC class II molecules differentially upregulates TNF beta gene expression in B cell lines of different MHC class II haplotypes

Although the production of selected cytokines by B cells is important for t heir regulation, little is known about MHC class II-induced cytokine expres sion in these cells. We designed the present studies to investigate MHC cla ss II-mediated TNF-beta gene expression in 19 EBV-transformed homozygote B cell lines at similar stage of differentiation but presenting different MHC class II haplotypes. Our results demonstrate that in contrast to PMA, enga gement of MHC class II with staphylococcal enterotoxin A (SEA), a natural l igand, or with anti-HLA-DR mAb L243, stimulates TNF-beta gene expression in some but not all B cell lines. The differential stimulation of TNF-beta ge ne expression via MHC class II was not due to the cells MHC class II expres sion level, nor to their capacity to bind the ligands as evidenced by SEA b inding affinity studies. Together these results demonstrate that ligation o f MHC class II molecules can stimulate TNF-beta gene expression in a B cell line-dependent manner. The differential cytokine gene expression might be due to an influence of MNC class II haplotype either by a linkage disequili brium with TNF-beta gene or by a differential association with effector or cell surface molecules. Human Immunology. 60, 312-322 (1999), (C) American Society for Histocompatibility and Immunogenetics, 1999, Published by Elsev ier Science Inc.